The invention relates to methods for identifying nucleic acid sequences that modulate the function of a cell, by the use of post-transcriptional gene silencing.
Double stranded RNA (dsRNA) has been shown to induce sequence-specific gene silencing in a number of different organisms. Gene silencing can occur through various mechanisms, one of which is post-transcriptional gene silencing (PTGS). In post-transcriptional gene silencing, transcription of the target locus is not affected, but the RNA half-life is decreased. The mechanisms by which PTGS occurs are not yet clear. Exogenous dsRNA has been shown to act as a potent inducer of PTGS in nematodes, trypanosomes, and insects. In addition, studies in C. elegans and Drosophila show that a few molecules of dsRNA per cell are sufficient to trigger a PTGS response. Furthermore, studies in mice have demonstrated that dsRNA can interfere with the expression of genes in mouse embryos.
There exists a need to identify molecules that selectively regulate the expression of genes in vertebrate cells without the associated toxicity of the interferon response. Such regulation should allow the downregulation of expression from genes whose gene products are detrimental to the cells.